Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles

International Journal of Pharmaceutics
Michael A CollierKristy M Ainslie

Abstract

Leishmaniasis is a disease caused by parasites of Leishmania sp., which effects nearly 12 million people worldwide and is associated with treatment complications due to widespread parasite resistance toward pathogen-directed therapeutics. The current treatments for visceral leishmaniasis (VL), the systemic form of the disease, involve pathogen-mediated drugs and have long treatment regimens, increasing the risk of forming resistant strains. One way to limit emergence of resistant pathogens is through the use of host-mediated therapeutics. The host-mediated therapeutic AR-12, which is FDA IND-approved for cancer treatment, has shown activity against a broad spectrum of intracellular pathogens; however, due to hydrophobicity and toxicity, it is difficult to reach therapeutic doses. We have formulated AR-12 into microparticles (AR-12/MPs) using the novel biodegradable polymer acetalated dextran (Ace-DEX) and used this formulation for the systemic treatment of VL. Treatment with AR-12/MPs significantly reduced liver, spleen, and bone marrow parasite loads in infected mice, while combinatorial therapies with amphotericin B had an even more significant effect. Overall, AR-12/MPs offer a unique, host-mediated therapy that could signif...Continue Reading

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Citations

Sep 21, 2016·Virulence·Kristie D Goughenour, Chad A Rappleye
Dec 16, 2017·Scientific Reports·Basant A AbdulrahmanHermann M Schatzl
Jun 3, 2020·Antimicrobial Agents and Chemotherapy·Shaoyan ZhangHaiqing Chu
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Jun 6, 2021·FEMS Microbiology Letters·M Shamim Hasan ZahidKristy M Ainslie

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